In this application for continuation of the MADRC, we propose to initiate new projects and extend two ongoing projects and maintain research cores. All projects involve investigations of Alzheimer's disease (AD) and AD mimics. The proposed projects include positron emission tomography (PET) studies of glucose metabolism and monoaminergic pathways in AD and dementia with Lewy disease (DLB); presynaptic neurochemical markers in AD, Parkinson's disease, and DLB; strategies for inhibition of Abeta protein aggregation; protein-protein interactions in amyloid precursor protein processing; and telephone counseling intervention to promote caregiver self-care behavior. Pilot projects are included in the proposal to stimulate innovative research in AD. The proposed Clinical, Neuropathology, Education and Information Transfer, and Biostatistics Cores will support these and a large number of other continuing and externally funded AD projects. Two successful satellite diagnostic and treatment centers in Detroit and Norther Michigan will continued to recruit under-represented urban, predominantly African American, and rural-resident patients to research studies The scientific approaches utilize major strengths in neurology and neuroscience at the longitudinal studies with autopsy verification, biostatistics, PET, molecular biology, molecular pharmacology, and survey research. The MADRC interacts with multiple components of the University to achieve its scientific and educational objectives, particularly the Schools of Medicine, Public Health, and Nursing, the Pepper Older Americans Independence Center, the Institute of Gerontology, the Geriatrics Center, and the Geriatric Research Education and Clinical Center at the Ann Arbor Veterans Medical Center. It collaborates with other ADCs on research projects and in datasharing. It plays a leadership role in statewide dementia initiatives and works closely with Michigan chapters of the Alzheimer Association. The scientific program proposed involves interdisciplinary collaboration of scientists and educators with many backgrounds and a strong training environment for predoctoral and postdoctoral students, medical students, and visiting scholars.